LncRNA SNHG3/miRNA-151a-3p/RAB22A axis regulates invasion and migration of osteosarcoma.

To elucidate the potential function of lncRNA SNHG3 in the development of osteosarcoma. Quantitative real-time polymerase chain reaction was conducted for detection of SNHG3, miRNA-151a-3p and RAB22 A in osteosarcoma tissues and cells. Receiver operating characteristic curve was introduced to analyze the diagnostic potential of SNHG3 in osteosarcoma. Correlation between SNHG3 expression and the overall survival of osteosarcoma patients was evaluated using Kaplan-Meier method. Invasive and migratory potentials of osteosarcoma cells were examined by Transwell assay. Furthermore, dual-luciferase reporter gene assay, RNA-pull down and RIP assay were used to verify the binding of SNHG3/RAB22 A to miRNA-151a-3p. The function of SNHG3/miRNA-151a-3p/RAB22 A axis in osteosarcoma was finally confirmed by rescue experiments. SNHG3 and RAB22 A were highly expressed in osteosarcoma patients, while miRNA-151a-3p was lowly expressed. The overall survival of osteosarcoma patients with high expression of SNHG3 was shorter than those with low expression. SNHG3 overexpression markedly promoted invasive and migratory potentials of osteosarcoma cells. Through dual-luciferase reporter gene assay, both SNHG3 and RAB22 A could bind to miRNA-151a-3p. RAB22 A expression was positively regulated by SNHG3, but negatively regulated by miRNA-151a-3p. Finally, rescue experiments confirmed that RAB22 A overexpression could reverse the promotive effects of miRNA-151a-3p knockdown on invasive and migratory potentials of osteosarcoma cells. SNHG3 is highly expressed in osteosarcoma, and promotes the invasive and migratory potentials of osteosarcoma cells by absorbing miRNA-151a-3p to upregulate RAB22 A expression.

[1]  C. Bauvy,et al.  Glucose persistence on high-mannose oligosaccharides selectively inhibits the macroautophagic sequestration of N-linked glycoproteins. , 2000, The Biochemical journal.

[2]  Bin Xu,et al.  Long non-coding RNA MALAT1 acts as a competing endogenous RNA to promote malignant melanoma growth and metastasis by sponging miR-22 , 2016, Oncotarget.

[3]  G. Siegal,et al.  Osteosarcoma: anatomic and histologic variants. , 2006, American journal of clinical pathology.

[4]  Xuhui Zhou,et al.  MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway , 2015, Tumor Biology.

[5]  P. Pandolfi,et al.  The multilayered complexity of ceRNA crosstalk and competition , 2014, Nature.

[6]  Wei Li,et al.  Overexpression of lncRNA UCA1 promotes osteosarcoma progression and correlates with poor prognosis , 2016, Journal of bone oncology.

[7]  Long Yu,et al.  Identification and characterization of nine novel human small GTPases showing variable expressions in liver cancer tissues. , 2002, Gene expression.

[8]  Qiang Zhang,et al.  Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[9]  Lisa Mirabello,et al.  International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons , 2009, International journal of cancer.

[10]  D. Shen,et al.  Clinical implication of long noncoding RNA 91H expression profile in osteosarcoma patients , 2016, OncoTargets and therapy.

[11]  Pier Paolo Pandolfi,et al.  ceRNA cross-talk in cancer: when ce-bling rivalries go awry. , 2013, Cancer discovery.

[12]  Jun Li,et al.  The long non-coding RNA SNHG3 functions as a competing endogenous RNA to promote malignant development of colorectal cancer , 2017, Oncology reports.

[13]  Maite Huarte.  The emerging role of lncRNAs in cancer , 2015, Nature Medicine.

[14]  Harald Stenmark,et al.  The small GTPase Rab22 interacts with EEA1 and controls endosomal membrane trafficking. , 2002, Journal of cell science.

[15]  Yubo Gao,et al.  Socioeconomic measures influence survival in osteosarcoma: an analysis of the National Cancer Data Base. , 2017, Cancer epidemiology.

[16]  J. Mattick,et al.  Long noncoding RNAs and the genetics of cancer , 2013, British Journal of Cancer.

[17]  C. Pirker,et al.  Seven novel and stable translocations associated with oncogenic gene expression in malignant melanoma. , 2005, Neoplasia.

[18]  N. Raikhel,et al.  Arabidopsis ribosomal proteins control vacuole trafficking and developmental programs through the regulation of lipid metabolism , 2014, Proceedings of the National Academy of Sciences.

[19]  P. Pandolfi,et al.  A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language? , 2011, Cell.

[20]  Li Liu,et al.  SNHG3 correlates with malignant status and poor prognosis in hepatocellular carcinoma , 2016, Tumor Biology.

[21]  Z. Bi,et al.  Long noncoding RNA FGFR3-AS1 promotes osteosarcoma growth through regulating its natural antisense transcript FGFR3 , 2016, Molecular Biology Reports.

[22]  Ming Sun,et al.  Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer , 2014, Molecular Cancer.

[23]  L. Mirabello,et al.  Osteosarcoma incidence and survival rates from 1973 to 2004 , 2009, Cancer.

[24]  A. Chinnaiyan,et al.  The emergence of lncRNAs in cancer biology. , 2011, Cancer discovery.